Protein chemical synthesis by serine and threonine ligation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 17; pp. 6657 - 6662
• Main Authors: Zhang, Yinfeng, Xu, Ci, Lam, Hiu Yung, Lee, Chi Lung, Li, Xuechen
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 23.04.2013; National Acad Sciences
• Subjects: Acetals; Acid Anhydride Hydrolases - chemical synthesis; Acylphosphatase; Aldehydes - chemistry; Amines; Amino acids; Animals; Chemical synthesis; Chemicals; Chromatography, High Pressure Liquid; Corticotropin-Releasing Hormone - chemical synthesis; Erythrocytes; Esters; Humans; Ligation; Mass Spectrometry; Molecular Structure; Peptides; Peptides - chemistry; Physical Sciences; Protein Engineering - methods; Proteins; Serine - chemistry; Sheep; Teriparatide - chemical synthesis; Thiols; Threonine - chemistry
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1221012110

An efficient method has been developed for the salicylaldehyde ester-mediated ligation of unprotected peptides at serine (Ser) or threonine (Thr) residues. The utility of this peptide ligation approach has been demonstrated through the convergent syntheses of two therapeutic peptides––ovine-corticoliberin and Forteo––and the human erythrocyte acylphosphatase protein (∼11 kDa). The requisite peptide salicylaldehyde ester precursor is prepared in an epimerization-free manner via Fmoc–solid-phase peptide synthesis.